4,5-Dicaffeoylquinic Acid

4,5-Dicaffeoylquinic Acid at a Glance

4,5-Dicaffeoylquinic acid — better known as isochlorogenic acid C — is a dicaffeoylquinic acid: a molecule of quinic acid esterified with two caffeic-acid (caffeoyl) units, at the 4- and 5-positions. It belongs to the wider chlorogenic-acid / caffeoylquinic-acid family and is one of three positional “isochlorogenic acid” isomers, alongside 3,5-dicaffeoylquinic acid (isochlorogenic acid A) and 3,4-dicaffeoylquinic acid (isochlorogenic acid B). It is a close relative of the mono-ester chlorogenic acid and shares the same reactive caffeic acid backbone, and it is a positional cousin of cynarin (1,5-di-CQA).

It occurs across a range of edible and medicinal plants — yerba maté, sweet potato leaf, honeysuckle flower, chicory, chrysanthemum and various Artemisia — so most human exposure is dietary and low-level.

The research picture is preclinical but genuinely present: unlike many minor phenolics, 4,5-di-CQA has been studied as the isolated molecule in cell and rodent models for antioxidant, anti-inflammatory, antiviral, lipid-lowering and antiproliferative effects. What it does not yet have is any human clinical trial, and its intact oral bioavailability is modest — so the in-vitro potencies should be read with that caveat.

What It's Used For

The distinctive feature of this molecule’s evidence base is that a fair share of it uses purified 4,5-di-CQA / isochlorogenic acid C itself, not just the extracts it comes in. That is a real strength for a compound this far down the phenolic hierarchy. The ceiling is that everything remains cell-culture and animal work — there are no human trials — and the compound’s own pharmacokinetics (modest bioavailability, heavy metabolism) temper how far the in-vitro numbers translate.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. Every row here is preclinical (no human data), so the scores rank depth of laboratory evidence, not clinical proof; read the per-row basis.

01Anti-Inflammatory (NF-κB/MAPK)Shaky42%Isolated compound in macrophages + rat model; OA chondroprotection ^{2,3Reference 2Jang G et al. · 2021AnimalAnti-inflammatory effect of 4,5-dicaffeoylquinic acid on RAW264.7 cells and a rat model of inflammationView study →Reference 3Jang G et al. · 2022Chondroprotective effects of 4,5-dicaffeoylquinic acid in osteoarthritis through NF-κB signaling inhibitionView study →}

02Antioxidant / CytoprotectionShaky40%Isolated compound; SIRT3–SOD2 + glutathione redox restoration ^{4,10Reference 4Li M et al. · 2025AnimalIsochlorogenic acid C protects mouse embryonic fibroblast cells from oxidative damage via restoring SIRT3-SOD2 activityView study →Reference 10Cao Z et al. · 2017Isochlorogenic acid C prevents enterovirus 71 infection via modulating redox homeostasis of glutathioneView study →}

03AntiviralShaky38%Isolated compound vs enterovirus 71, cell + mouse; RSV extract signal ^{10Reference 10Cao Z et al. · 2017Isochlorogenic acid C prevents enterovirus 71 infection via modulating redox homeostasis of glutathioneView study →}

04Hepatoprotective / Lipid-LoweringShaky34%Isolated compound; reverse cholesterol transport in high-fat-diet mice ^{5Reference 5Zheng L et al. · 2022Isochlorogenic acid C alleviates high-fat diet-induced hyperlipemia by promoting cholesterol reverse transportView study →}

05Antiproliferative (Cancer Cells)Shaky28%Isolated compound, in-vitro only (prostate, breast) ^{6,8Reference 6Lodise O et al. · 2019Inhibition of prostate cancer cells by 4,5-dicaffeoylquinic acid through cell cycle arrestView study →Reference 8Yu JK et al. · 2018Isochlorogenic acid C reverses epithelial-mesenchymal transition via down-regulation of EGFR pathway in MDA-MB-231 cellsView study →}

06Neuroprotective / Metabolic (extract)Shaky22%Mostly whole-extract signals where it is one CQA among several ^{1,7,9Reference 1Xu JY et al. · 2025Isochlorogenic acid C alleviates allergic asthma via interactions between its bioactive form and the gut microbiomeView study →Reference 7Chu JMT et al. · 2022Sigesbeckia orientalis L. derived active fraction ameliorates perioperative neurocognitive disorders through alleviating hippocampal neuroinflammationView study →Reference 9Yin XL et al. · 2018AnimalGynura divaricata rich in 3,5-/4,5-dicaffeoylquinic acid and chlorogenic acid reduces islet cell apoptosis and improves pancreatic function in type 2 diabetic miceView study →}

Mechanisms

The unifying thread is redox and NF-κB: two caffeoyl catechols give strong radical-scavenging and glutathione-restoring chemistry, which feeds an anti-inflammatory NF-κB/MAPK signature that recurs across the inflammation, antiviral and metabolic models.

Pharmacokinetics

Like other dicaffeoylquinic acids, 4,5-di-CQA is a large, polar polyphenol with modest intact oral bioavailability — the one study to measure isochlorogenic acid C directly reported ~14.4–16.9%, and framed part of its activity as depending on gut-microbiome bioactivation into downstream metabolites ^{1Reference 1Xu JY et al. · 2025Isochlorogenic acid C alleviates allergic asthma via interactions between its bioactive form and the gut microbiomeView study →}. A rat metabolite study found the compound is extensively metabolised — roughly fifteen plasma and sixteen urinary metabolites via methylation, glucuronidation and sulfation — consistent with heavy phase-II conjugation and microbial hydrolysis to caffeic and quinic acid fragments ^{11Reference 11Zhan MR et al. · 2020AnimalZhan MR, et al. (2020). [Analysis of metabolites of 4,5-dicaffeoylquinic acid in rat plasma and urine based on LC-MS]. Zhongguo Zhong Yao Za Zhi. https://pubmed.ncbi.nlm.nih.gov/32237323/View study →}. The practical implication is the standard caffeoylquinic caveat: plasma levels of the intact molecule are low relative to the concentrations used in cell assays, so high-potency in-vitro results do not translate one-to-one to oral exposure.

Clinical Trials

There are no human clinical trials of isolated 4,5-dicaffeoylquinic acid / isochlorogenic acid C. The entire evidence base is preclinical — isolated-compound cell and rodent studies plus whole-extract animal work.

Last checked: July 2026.

Isolate vs. Plant Studies

Unusually for a minor phenolic, a solid block of this molecule’s data uses the purified compound: the anti-inflammatory ^{2Reference 2Jang G et al. · 2021AnimalAnti-inflammatory effect of 4,5-dicaffeoylquinic acid on RAW264.7 cells and a rat model of inflammationView study →}, chondroprotective ^{3Reference 3Jang G et al. · 2022Chondroprotective effects of 4,5-dicaffeoylquinic acid in osteoarthritis through NF-κB signaling inhibitionView study →}, antioxidant/SIRT3 ^{4Reference 4Li M et al. · 2025AnimalIsochlorogenic acid C protects mouse embryonic fibroblast cells from oxidative damage via restoring SIRT3-SOD2 activityView study →}, antiviral EV71 ^{10Reference 10Cao Z et al. · 2017Isochlorogenic acid C prevents enterovirus 71 infection via modulating redox homeostasis of glutathioneView study →}, hepatoprotective ^{5Reference 5Zheng L et al. · 2022Isochlorogenic acid C alleviates high-fat diet-induced hyperlipemia by promoting cholesterol reverse transportView study →} and anticancer ^{6,8Reference 6Lodise O et al. · 2019Inhibition of prostate cancer cells by 4,5-dicaffeoylquinic acid through cell cycle arrestView study →Reference 8Yu JK et al. · 2018Isochlorogenic acid C reverses epithelial-mesenchymal transition via down-regulation of EGFR pathway in MDA-MB-231 cellsView study →} studies all tested isolated 4,5-di-CQA (or isochlorogenic acid C, the same molecule). That is a genuine strength — it means the effects are not merely inferred from a complex extract. The remaining results are extract-level: the Sigesbeckia neurocognitive fraction ^{7Reference 7Chu JMT et al. · 2022Sigesbeckia orientalis L. derived active fraction ameliorates perioperative neurocognitive disorders through alleviating hippocampal neuroinflammationView study →}, the Gynura divaricata antidiabetic extract ^{9Reference 9Yin XL et al. · 2018AnimalGynura divaricata rich in 3,5-/4,5-dicaffeoylquinic acid and chlorogenic acid reduces islet cell apoptosis and improves pancreatic function in type 2 diabetic miceView study →} and the Lonicera anti-RSV fraction, where 4,5-di-CQA co-occurs with chlorogenic acid and its 3,5-/3,4-isomers and its individual share is not resolved. Across both categories the vehicle is preclinical — no human trial exists in either form.

Its Role in Plants

Dicaffeoylquinic acids are products of the phenylpropanoid pathway. Plants build them by esterifying quinic acid with caffeoyl-CoA through hydroxycinnamoyl-CoA transferase enzymes (HCT/HQT); a first caffeoylation gives chlorogenic acid, and a second caffeoylation at another quinic-acid hydroxyl gives a dicaffeoylquinic acid such as the 4,5-isomer. Functionally these phenolics serve as antioxidant and defensive metabolites — quenching reactive oxygen, absorbing UV, and deterring herbivores and pathogens. This is plant biology, not human pharmacology, and should not be read as evidence of a medicinal effect.

Prevalence in Nature

4,5-Dicaffeoylquinic acid is one of the isochlorogenic acids distributed across many Asteraceae, Convolvulaceae and Caprifoliaceae plants. It is a recognised phenolic of yerba maté (Ilex paraguariensis), where the caffeoylquinic-acid family collectively reaches ~10–16% of dried leaf, and of sweet potato leaf (Ipomoea batatas), where purple-fleshed cultivars carry comparatively high 4,5-di-CQA ^{12Reference 12Chiu CH et al. · 2022Analysis of chlorogenic acid in sweet potato leaf extractsView study →}. Japanese honeysuckle (Lonicera japonica) flower buds and chrysanthemum (Chrysanthemum morifolium) are rich enough to serve as the standard sources for isolating the compound by counter-current and preparative chromatography ^{13Reference 13Guo W et al. · 2015Isolation of isochlorogenic acid isomers in flower buds of Lonicera japonica by high-speed counter-current chromatography and preparative high performance liquid chromatographyView study →}. It is further reported in chicory (Cichorium intybus), various Artemisia, Laggera, Erigeron breviscapus and Gynura divaricata ^{9Reference 9Yin XL et al. · 2018AnimalGynura divaricata rich in 3,5-/4,5-dicaffeoylquinic acid and chlorogenic acid reduces islet cell apoptosis and improves pancreatic function in type 2 diabetic miceView study →}.

It is the 4,5-positional isomer of the isochlorogenic-acid set — distinct from 3,5-dicaffeoylquinic acid (isochlorogenic acid A) and 3,4-dicaffeoylquinic acid (isochlorogenic acid B). No single, reliably measured percentage is resolved specifically to the 4,5-isomer across these sources; most assays report the caffeoylquinic acids as a group, so the source-by-source quantities remain a gap to chase.

Discovery & Synthesis

4,5-Dicaffeoylquinic acid was not “discovered” as a headline molecule so much as characterised within the broader chlorogenic-acid chemistry of the mid-20th century, once the three isochlorogenic-acid isomers (A = 3,5-, B = 3,4-, C = 4,5-) were resolved and assigned by the IUPAC quinic-acid numbering. The name isochlorogenic acid C dates from that isomer-mapping era.

Manufacture today is by extraction, not synthesis. The compound is obtained from phenolic-rich botanicals — most often honeysuckle flower buds or chrysanthemum — using high-speed counter-current chromatography and preparative HPLC to separate the closely related isochlorogenic isomers to high purity ^{13Reference 13Guo W et al. · 2015Isolation of isochlorogenic acid isomers in flower buds of Lonicera japonica by high-speed counter-current chromatography and preparative high performance liquid chromatographyView study →}. Selective double-caffeoylation of quinic acid is chemically possible but regioselectivity between the 3-, 4- and 5-positions is difficult, so plant extraction remains the practical route for research-grade material.

Patents: not yet researched.

Toxicity & Safety

4,5-Dicaffeoylquinic acid carries a low toxicity flag. It is a dietary phenolic acid present in commonly consumed plants — yerba maté, sweet potato leaf, chicory and honeysuckle tea — and the caffeoylquinic-acid class it belongs to has a long history of food and beverage exposure without notable toxicity. No dedicated repeat-dose, genotoxicity or reproductive-toxicity dataset has been characterised for the isolated molecule, so safety here is inferred from its class and dietary background rather than demonstrated for the pure compound.

Safety at a Glance

✅ Low / no toxicity

• Dietary phenolic with low expected toxicity. Consumed routinely in maté, sweet potato leaf, chicory and honeysuckle preparations as part of the caffeoylquinic-acid family.
• No isolate safety package. Repeat-dose, genotoxicity, drug-interaction and reproductive-toxicity data for the pure compound are absent — safety is inferred, not established.
• Caffeoylquinic-acid allergenicity. Chlorogenic-type acids are documented (if uncommon) contact and respiratory sensitisers; the same class caution applies here.

No formal drug-interaction studies (CYP or transporter) have been reported for the isolated compound. Because caffeoylquinic acids are heavily conjugated by phase-II enzymes and hydrolysed by gut microbiota (see Pharmacokinetics), any interaction potential would most plausibly involve those routes, but this has not been assessed. Reproductive and developmental safety of the isolated molecule is uncharacterised; intake decisions belong to the herb or product page where exposure is set, not to this molecule page.

Dosage

There is no established or recommended human dose for isolated 4,5-dicaffeoylquinic acid. Every quantitative figure in the literature is a research dose in cells or animals — for example low-micromolar concentrations in the antiproliferative cell studies ^{6Reference 6Lodise O et al. · 2019Inhibition of prostate cancer cells by 4,5-dicaffeoylquinic acid through cell cycle arrestView study →} and milligram-per-kilogram oral dosing in the rodent anti-inflammatory, antiviral and lipid models ^{2,5,10Reference 2Jang G et al. · 2021AnimalAnti-inflammatory effect of 4,5-dicaffeoylquinic acid on RAW264.7 cells and a rat model of inflammationView study →Reference 5Zheng L et al. · 2022Isochlorogenic acid C alleviates high-fat diet-induced hyperlipemia by promoting cholesterol reverse transportView study →Reference 10Cao Z et al. · 2017Isochlorogenic acid C prevents enterovirus 71 infection via modulating redox homeostasis of glutathioneView study →}. Dietary exposure, by contrast, is incidental and low, arriving as one of several caffeoylquinic acids in maté, sweet potato leaf, chicory and honeysuckle preparations.

These are doses studied in research and are not a personal recommendation.

References

1. Xu JY, et al. (2025). Isochlorogenic acid C alleviates allergic asthma via interactions between its bioactive form and the gut microbiome. International Journal of Molecular Sciences. https://pubmed.ncbi.nlm.nih.gov/40430003/
2. Jang G, et al. (2021). Anti-inflammatory effect of 4,5-dicaffeoylquinic acid on RAW264.7 cells and a rat model of inflammation. Nutrients. https://pubmed.ncbi.nlm.nih.gov/34684537/
3. Jang G, et al. (2022). Chondroprotective effects of 4,5-dicaffeoylquinic acid in osteoarthritis through NF-κB signaling inhibition. Antioxidants (Basel). https://pubmed.ncbi.nlm.nih.gov/35326137/
4. Li M, et al. (2025). Isochlorogenic acid C protects mouse embryonic fibroblast cells from oxidative damage via restoring SIRT3-SOD2 activity. Bioorganic Chemistry. https://pubmed.ncbi.nlm.nih.gov/40664151/
5. Zheng L, et al. (2022). Isochlorogenic acid C alleviates high-fat diet-induced hyperlipemia by promoting cholesterol reverse transport. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/35959429/
6. Lodise O, et al. (2019). Inhibition of prostate cancer cells by 4,5-dicaffeoylquinic acid through cell cycle arrest. Prostate Cancer. https://pubmed.ncbi.nlm.nih.gov/31263600/
7. Chu JMT, et al. (2022). Sigesbeckia orientalis L. derived active fraction ameliorates perioperative neurocognitive disorders through alleviating hippocampal neuroinflammation. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/35370714/
8. Yu JK, et al. (2018). Isochlorogenic acid C reverses epithelial-mesenchymal transition via down-regulation of EGFR pathway in MDA-MB-231 cells. Anticancer Research. https://pubmed.ncbi.nlm.nih.gov/29599331/
9. Yin XL, et al. (2018). Gynura divaricata rich in 3,5-/4,5-dicaffeoylquinic acid and chlorogenic acid reduces islet cell apoptosis and improves pancreatic function in type 2 diabetic mice. Nutrition & Metabolism (London). https://pubmed.ncbi.nlm.nih.gov/30337946/
10. Cao Z, et al. (2017). Isochlorogenic acid C prevents enterovirus 71 infection via modulating redox homeostasis of glutathione. Scientific Reports. https://pubmed.ncbi.nlm.nih.gov/29176678/
11. Zhan MR, et al. (2020). [Analysis of metabolites of 4,5-dicaffeoylquinic acid in rat plasma and urine based on LC-MS]. Zhongguo Zhong Yao Za Zhi. https://pubmed.ncbi.nlm.nih.gov/32237323/
12. Chiu CH, et al. (2022). Analysis of chlorogenic acid in sweet potato leaf extracts. Plants (Basel). https://pubmed.ncbi.nlm.nih.gov/35956541/
13. Guo W, et al. (2015). Isolation of isochlorogenic acid isomers in flower buds of Lonicera japonica by high-speed counter-current chromatography and preparative high performance liquid chromatography. Journal of Chromatography B. https://pubmed.ncbi.nlm.nih.gov/25596381/
14. Li X, et al. (2025). Dipeptidyl peptidase 4 (DPP4) exacerbates osteoarthritis progression in an enzyme-independent manner. Advanced Science (Weinheim). https://pubmed.ncbi.nlm.nih.gov/39680708/
15. Liang Y, et al. (2023). Analyzing the material basis of anti-RSV efficacy of Lonicerae japonicae Flos based on the PK-PD model. Molecules. https://pubmed.ncbi.nlm.nih.gov/37764214/

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